Two Cheers and a Pint of Worry: An On-Line Course in Political and Social Philosophy

During the past decade there have been numerous efforts to reinvigorate distance education; some of these have involved video technology, but others have made use of computers and advances in the design of computer software. In 1995, the State University of New York, funded by a major grant from the Sloan Foundation, embarked upon the creation of an "on-line" learning program--a set of asynchronous and distance learning courses delivered solely via computer. In what follows, I detail the genesis and structure of a course in political and social philosophy that I designed (and taught) for this project. After some preliminary comments on the "virtual classroom”. I illustrate the design of the course, and then offer a brief qualitative assessment. I close the essay with some cautionary reflections on computer-mediated education. Athough my initial skepticism about such courses has been modified, I still believe that there is something valuable about the direct, face-to-face, encounter of teacher and student that is not easily compensated for in computer-mediated learning

Targeting Dendritic Cells in vivo for Cancer Therapy

Monoclonal antibodies that recognize cell surface molecules have been used deliver antigenic cargo to dendritic cells (DC) for induction of immune responses. The encouraging anti-tumor immunity elicited using this immunization strategy suggests its suitability for clinical trials. This review discusses the complex network of DC, the functional specialization of DC subsets, the immunological outcomes of targeting different DC subsets and their cell surface receptors, and the requirements for the induction of effective anti-tumor CD4 and CD8 T cell responses that can recognize tumor-specific antigens. Finally, we review preclinical experiments and the progress toward targeting human DC in vivo

Broadening the scope of the modified-Julia reaction : a mild and stereoselective method for the synthesis of (Z)-configurated α,β-unsaturated lactones

An intramolecular variant of the modified-Julia olefination was demonstrated by the synthesis of α,β-unsaturated lactones in a mild and (Z)-selective fashion. The lynchpin reagent (benzothiazol-2-sulfonyl) acetic acid was synthesized in a straightforward fashion in 86% overall yield from commercially available 2-mercaptobenzothiazole via conversion to ethyl (benzothiazol-2-ylthio)acetate by base mediated alkylation with ethyl chloroactetate; saponification of the ester to (1,3-benzothiazol-2-ylthio)acetic acid; and, oxidation by ammonium molybdate and H₂O₂ to afford the key sulfonyl acid reagent. Through the use of an efficient dicyclohexylcarbodiimide coupling reaction, the acetic acid derivative was condensed with a series of ω-alkenyl carbinols to form the corresponding ω-alkenyl (benzothiazol-2-sulfonyl)acetates in moderate to excellent yields (60 – 94%). The esters were then subjected to ozonolysis conditions (O₃ in CH₂Cl₂) and, after subsequent reduction of the ozonide with dimethyl sulfide, the carboxaldehyde intermediates were immediately subjected to 1,8-diazabicycloundec-7-ene in CH₂Cl₂ (-78 °C to rt) to effect cyclic alkene formation. Successful production of the α,β-unsaturated lactones was observed for a variety of ring sizes (7, 12, 13, and 19) in moderate yields (30 – 45%), but comparable to other methods for lactone synthesis. Aldol condensation products resulting from the elimination of H₂O from the putative anti-β-alkoxy-benzothiazol-sulfones intermediates were also obtained from the smaller rings sizes, albeit in low yields (2 – 4%). The reaction conditions proved to be ideal for these simple substrates. Significantly, biasing factors such as Thorpe-Ingold effects were not required to aid macrocyclic lactone formation. The targeted α,β-unsaturated lactones were generated stereoselectively with predominantly (Z)-configuration (Z:E ≥ 85:15) in all cases examined

Designer Reagents for Mass Spectrometry-Based Proteomics: Clickable Cross-Linkers for Elucidation of Protein Structures and Interactions

We present novel homobifunctional amine-reactive clickable cross-linkers (CXLs) for investigation of three-dimensional protein structures and protein–protein interactions (PPIs). CXLs afford consolidated advantages not previously available in a simple cross-linker, including (1) their small size and cationic nature at physiological pH, resulting in good water solubility and cell-permeability, (2) an alkyne group for bio-orthogonal conjugation to affinity tags via the click reaction for enrichment of cross-linked peptides, (3) a nucleophilic displacement reaction involving the 1,2,3-triazole ring formed in the click reaction, yielding a lock-mass reporter ion for only clicked peptides, and (4) higher charge states of cross-linked peptides in the gas-phase for augmented electron transfer dissociation (ETD) yields. Ubiquitin, a lysine-abundant protein, is used as a model system to demonstrate structural studies using CXLs. To validate the sensitivity of our approach, biotin-azide labeling and subsequent enrichment of cross-linked peptides are performed for cross-linked ubiquitin digests mixed with yeast cell lysates. Cross-linked peptides are detected and identified by collision induced dissociation (CID) and ETD with linear quadrupole ion trap (LTQ)-Fourier transform ion cyclotron resonance (FTICR) and LTQ-Orbitrap mass spectrometers. The application of CXLs to more complex systems (e.g., in vivo cross-linking) is illustrated by Western blot detection of Cul1 complexes including known binders, Cand1 and Skp2, in HEK 293 cells, confirming good water solubility and cell-permeability

Minimal Brownian Ratchet: An Exactly Solvable Model

We develop an exactly-solvable three-state discrete-time minimal Brownian ratchet (MBR), where the transition probabilities between states are asymmetric. By solving the master equations we obtain the steady-state probabilities. Generally the steady-state solution does not display detailed balance, giving rise to an induced directional motion in the MBR. For a reduced two-dimensional parameter space we find the null-curve on which the net current vanishes and detailed balance holds. A system on this curve is said to be balanced. On the null-curve, an additional source of external random noise is introduced to show that a directional motion can be induced under the zero overall driving force. We also indicate the off-balance behavior with biased random noise.Comment: 4 pages, 4 figures, RevTex source, General solution added. To be appeared in Phys. Rev. Let

Considering agency and data granularity in the design of visualization tools

The Ecuadorian Government supports Gonzalo Gabriel Méndez through a SENESCYT scholarship.Previous research has identified trade-offs when it comes to designing visualization tools. While constructive “bottom-up” tools promote a hands-on, user-driven design process that enables a deep understanding and control of the visual mapping, automated tools are more efficient and allow people to rapidly explore complex alternative designs, often at the cost of transparency. We investigate how to design visualization tools that support a user-driven, transparent design process while enabling efficiency and automation, through a series of design workshops that looked at how both visualization experts and novices approach this problem. Participants produced a variety of solutions that range from example-based approaches expanding constructive visualization to solutions in which the visualization tool infers solutions on behalf of the designer, e.g., based on data attributes. On a higher level, these findings highlight agency and granularity as dimensions that can guide the design of visualization tools in this space.Postprin

Anthropogenic, direct pressures on coastal wetlands

Coastal wetlands, such as saltmarshes and mangroves that fringe transitional waters, deliver important ecosystem services that support human development. Coastal wetlands are complex social-ecological systems that occur at all latitudes, from polar regions to the tropics. This overview covers wetlands in five continents. The wetlands are of varying size, catchment size, human population and stages of economic development. Economic sectors and activities in and around the coastal wetlands and their catchments exert multiple, direct pressures.Chinese Academy of Sciences (CAS-YIC) scholarship and SKLECECNU project 111 scholarship<, Natural Resources Canada contribution no. 20200070; Fundação para a Ciência e a Tecnologia (FCT) Scientific Employment Stimulus Programme (CEECIND/01635/2017). and (CEECIND/00095/2017), (UID/MAR/00350/2019CIMA) and (UID/MAR/04292/2019)info:eu-repo/semantics/publishedVersio

Energy gain of wetted-foam implosions with auxiliary heating for inertial fusion studies

Low convergence ratio implosions (where wetted-foam layers are used to limit capsule convergence, achieving improved robustness to instability growth) and auxiliary heating (where electron beams are used to provide collisionless heating of a hotspot) are two promising techniques that are being explored for inertial fusion energy applications. In this paper, a new analytic study is presented to understand and predict the performance of these implosions. Firstly, conventional gain models are adapted to produce gain curves for fixed convergence ratios, which are shown to well-describe previously simulated results. Secondly, auxiliary heating is demonstrated to be well understood and interpreted through the burn-up fraction of the deuterium-tritium fuel, with the gradient of burn-up with respect to burn-averaged temperature shown to provide good qualitative predictions of the effectiveness of this technique for a given implosion. Simulations of auxiliary heating for a range of implosions are presented in support of this and demonstrate that this heating can have significant benefit for high gain implosions, being most effective when the burn-averaged temperature is between 5 and 20 keV

Human G Protein–Coupled Receptor Gpr-9-6/Cc Chemokine Receptor 9 Is Selectively Expressed on Intestinal Homing T Lymphocytes, Mucosal Lymphocytes, and Thymocytes and Is Required for Thymus-Expressed Chemokine–Mediated Chemotaxis

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein–coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti–GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory α4β7high intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen–positive (CLA+) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic α4β7−CLA− memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti–GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response